Long-Term Epoprostenol Therapy in Pulmonary Artery Hypertension

Abstract

Circ J 2009; 73: 523 -529 hronic epoprostenol infusion ameliorates the hemodynamics and prognosis of pulmonary artery hypertension (PAH), 1-5 which progresses early with an elevation in pulmonary artery pressure (PAP) and then shows a reduction in cardiac output (CO). 6 The sequence of the hemodynamic improvement after epoprostenol infusion therapy, however, has not been elucidated in detail.Some patients with PAH improve sufficiently to cease requiring further increases in the epoprostenol dosage (good responders), whereas others (poor responders) still require increasing doses. It is unclear what causes the difference in response to epoprostenol between good and poor responders. Moreover, the hemodynamic changes after ceasing incremental epoprostenol therapy are unclear.The primary purpose of the present study was to examine the differences in the hemodynamic response to epoprostenol therapy of good and poor responders treated with epoprostenol for 1 or more years. The secondary purpose was to investigate the hemodynamic course in good responders after cessation of incremental epoprostenol treatment. The third purpose was to clarify whether an increase in CO precedes lowering of the PAP, which reverses the progress in PAH. (Received December 16, 2007; revised manuscript received August 27, 2008; accepted October 26, 2008; released online January 29, 2009 Long-Term Epoprostenol Therapy in Pulmonary Artery Hypertension Sequence of Changes in Hemodynamic EffectsMasahito Sakuma, MD; Jun Demachi, MD*; Jun Nawata, MD**; Jun Suzuki, MD † ; Tohru Takahashi, MD † † ; Kunio Shirato, MD ‡ Background: Sequential changes in the hemodynamic effect of chronic epoprostenol therapy raise the following questions. Does an increase in cardiac output (CO) precede lowering of the pulmonary artery pressure (PAP) over the time course of improvement? What are the characteristics of good responders to chronic epoprostenol treatment? Methods and Results: Hemodynamics were evaluated by catheter examination. Most patients still alive after >1 year showed an increase in CO either with no change in mean PAP or accompanied by a decrease in mean PAP during increased dosing of epoprostenol. Immediately before cessation of the increase in epoprostenol dose in good responders, the ratio of total pulmonary resistance to total systemic resistance was low, and the pulmonary artery wedge pressure minus right atrial pressure was high compared with the newest data in poor responders. One year after fixing at the best dose of epoprostenol, the mean PAP further decreased. Conclusions:In good responders, pulmonary selectivity to epoprostenol is high, and the blood returning to the left-sided heart through the pulmonary circulation increases. Hemodynamics further improve, even after fixing at the best dose of epoprostenol. The present data did not show that an increase in CO precedes lowering of the PAP over the course of improvement. (Circ J 2009; 73: 523 -529)

Meta-Analysis of Randomized Controlled Trials on Treatment of Pulmonary Arterial Hypertension

“…It can enhance the concentration of cyclic guanosine monophosphate of pulmonary vascular smooth muscle cells through inhibiting PDE-5 and promote the function of endogenous nitric oxide. 20, 21 In addition, it has the effect of inhibiting vascular smooth muscle cell proliferation, 22 alleviating pulmonary vascular remodeling and thus attenuating PAH effectively.…”

Rapid Initiation of Intravenous Epoprostenol Infusion Is the Favored Option in Patients with Advanced Pulmonary Arterial Hypertension

“…The maximum dose-dependent epoprostenol efficacy in patients with PAH [ 12 , 17 ], and a dose-dependent reduction in PVR with epoprostenol IVI therapy [ 18 ] were previously reported in patients with PAH. However, there is no apparent evidence that the efficacy of epoprostenol also depends on the initiation schedule, despite anecdotal evidence from PAH specialists of the merits of rapid initiation.…”